You need to get calories from somewhere, should it be from carbohydrate or fat?

Tuesday, December 28, 2010

Anacetrapib and phytotoxins

Just starting to find a little time to post. This seems like a worthwhile snippet as a follow on to the anacetrapib post, easier to put up than the cooking epics on insulin and the liver, parts two onwards........

Ok, the usual recap:

First there was cholesterol. It was bad, life was simple.

Then came Good cholesterol, HDL battling the Bad cholesterol, LDL.

Then there was Good LDL, large buoyant battling with Really Bad LDL, small dense LDL, sdLDL.

Not only that but native LDL appears to be harmless, it's only oxidised LDL which is the killer, oxLDL.

So the evil sdLDL is only really evil because it is more easily oxidised than fluffier LDL. Maybe, but in general I tend to have glazed over by now, befuddled by the blur of the moving goal posts.

But just occasionally something does grab my attention, especially if it markedly deepens the hole being dug for itself by the lipid hypothesis, like anacetrapib.

It was thanks to Dr Davis that I grasped the concept of CETP inhibitors as eliminators of sdLDL. That's what they are. If you believe in the lipid hypothesis it must be pretty interesting to have a drug which virtually eliminates sdLDL while increasing the body count for cardiovascular deaths, even if 4 dead out of 808 vs 1 dead out of 804 does not reach statistical significance.

But the real gem from Dr D was the finding that anthocyanins are CETP inhibitors. You no longer need to sign up for the next anacetrapib trial to die of a heart attack in the cause of the lipid hypothesis. You can buy a do-it-yourself CETP inhibitor in the form of a purple plant dye.

EDIT pre posting: It always amazes me that someone as perceptive on blood glucose, and indirectly on blood insulin, as Dr Davis can still believe the lipid hypothesis. Really believe. Fascinating.

There now, we all know plants are all natural, healthy and safe. Perhaps that includes recreational plants like Deadly Nightshade, Nux Vomica and Henbane. As an alternative to anacetrapib you can only hope the anthocyanins don't work!

If they do work at least you might have the consolation that you died with cracking lipids.

"However, a similar decrease in protein oxidation [on flavonoid elimination], in 8-oxo-dG excretion and in the increased resistance of plasma lipoproteins to oxidation in the present study points to a more general relief of oxidative stress after depletion of flavonoid- and ascorbate-rich fruits and vegetables from the diet, contrary to common beliefs."

I actually rather like the therapeutic potential of anthocyanins. Although they are mildly toxic to humans, they are highly toxic to some gut pathogens, especially fungi and some biofilm-forming bacteria.

Anthocyanins are also relatively more toxic to cancer cells than normal human cells.

There is even an argument that the mild toxicity to humans can provide a beneficial hormesis. Hard to prove this of course ...

Ned's link is a good example of the argument for hormesis as I have seen it made. In the act of cleaning up the plant toxins, the body upregulates activities that also clean up other toxins, damaged proteins, or pathogens. So goes the theory. There is evidence for it but not so far as I am aware anything that would convince a skeptic that these beneficial effects outweigh the toxicity.

But I think the case that eating the berries is health improving for humans is reasonably strong, because of beneficial effects in the gut. In berries, anthocyanins and prebiotic fiber such as inulin modulate the gut flora in a favorable direction. As Ned's link says, only 5% of ingested anthocyanins enter the body; 95% stay in the gut. The dose in the body is too low to be highly toxic. The dose in the gut is toxic - to pathogens.

Again, this is a judgment call. But I think it would be rash to give up plant foods because they have toxins.

About the green tea/flavonoid-free paper: what data makes you conclude that the drop in oxidative damage was caused by a reduction in fruit consumption? Perhaps I missed something, but I cannot find any details in the paper about the participants' habitual diet. I can only derive that it contained some source of vitamin C (from Fig. 3).

In other words, we have a comparison of an unknown habitual diet (with some source of vitamin C) to 10 weeks on a well-specified diet (which was devoid of fruit and flavonoids). The well-specified diet caused a decrease in oxidative damage.Without details about the habitual diet, I think it's quite impossible to pinpoint the cause for the decrease in oxidative damage. Which is very unfortunate.

Like the investigators, we can speculate. Maybe the participants ate a lot of fruit prior to the intervention, and the fructose in the fruit was the cause of oxidative damage. But perhaps they just drank a lot of soft drinks, providing ample fructose for oxidative damage. Maybe they ate a lot of food fried in PUFA rich oils. Or some combination.

So, could you please expand on the reasons for your conclusion?Thanks.

This discussion is pretty funny. There is so little evidence for hormesis, but the evidence is compelling enough that we have a developed dose-response where we know we should eat one serving of fruit or vegetables per week? Hmm, we can't have our anthocyanins and eat them too!

Actually there is some solid evidence of hormesis in animal models and it will be pouring in over the next year or two I think. I'll post about this a bit after New Years's. Have a happy holiday everyone!

Agree, but remember that the hormetic curve has an inverted J-shape. Fruits arent essential for an optimal health. Its use is more flavor-wise. Nevertheless, a bowl of berries is healthier than a bowl of cheerios.

ROFL This study sounds like another dogmatic attempt to prove that most Vegans will die of Heart Attack. The truth? Fruit and Veggies are no more harmful then sleeping at night or feeding Men Soy. (See 2nd Truth below, for explanation.)

The Truth: More non-Vegans die from Heart Attacks each year eating their flavanoid free animal then Vegans do in 20 years on a Vegan diet.

The Truth: If Soy really caused men to be impotent, then why is the Japanese and the Chinese population so high? Or, do the researchers really think that Asian's with their high Soy content is immune?

Yep, you can bias your research and your results to prove anything you want. And, if you use critical thinking, you can even find the truth and reason out the erroneous conclusions those biased researchers make.

Bottom line: In my opinion, most researchers are biased and can't be trusted. Usually, they are paid to prove something true, that might not be true. Thankfully, we have the PCMA that proved how a Vegan diet didn't harm Kidneys, the ADA diet (all animal meats) did harm Kidneys, and the control diet (fish and chicken) only had some damage to kidneys. Bias? It wasn't biased. If it would have been biased, they would have found more kidney damage in the Control group in order to prove the Vegan diet. And, at least one of the Doctors involved grew up on Bacon fat in North Dakota.

Humans and our ancestors have been eating fruit for at least 55-65 million years. The probability that moderate consumption (<50g/day) of wild fruits is harmful to humans is therefore close to zero.

All traditional human societies actively seek out fruit as do most carnivores.

It is possible that anthocyanins are used primarily as pigments by plants. The antioxidant effects may simply be coincidental.

Most plants use sugars as energy reserves - not to attract animals. The plants with the highest sugar content - beets and sugar cane - do not produce edible fruits. These plants go to a lot of effort to protect their sugar stores from animals - buried tubers or tough stems.

Sugars are also used as effective anti-freezes by plants such as as potatoes and daffodils that must survive cold winters.

Antioxidants are unlikely to be intended to protect the plant against sugars. The vascular systems of plants are made of cellulose and lignin which do not react with carbohydrates.

There is typically an inverse relationship between sugar content and antioxidant content in plants.

Studies on isolated nutrients are absolutely worthless because they simply don't behave the same way as complete foods.

Peter, I have a question I'm hoping you can give me your opinion on: how serious do you think oxidized cholesterol in food is? I seem to remember you saying you cook your egg yolks whole, rather than scrambled to avoid this issue.

This study found 12.3% of sterols were oxidized in a sample of ghee: http://www.ncbi.nlm.nih.gov/pubmed/2887943?dopt=Abstract

Of course I wonder how browned some Indians like their ghee, compared to something like French clarified butter, which isn't usually as toasted.

I worry because I've been eating about 8 tablespoons of ghee a day in place of butter, trying to avoid casein. Maybe I will try using Kerrygold Irish butter which is grassfed and may have more A2 casein than American dairy and be less problematic... I wonder what the common breeds of cow are in Ireland?

No time for more but to Owen, I don't worry about oxidised sterols at all. We wouldn't accummulate them in Lp(a) unless they are useful. I have a stack of links from Leib's work on THINCS showing oxidised sterols are great solubulisers of crystaline cholesterol (which appears to be bad). He makes an interesting case...

Peter, sorry if this is a weird question, but do you find you are still regular (IE having at least a bowel movement daily) on this type of diet? Did it take a while to adjust to, or do you think that most of the bacteria die off so you dont produce as much waste (since it is mainly water and bacteria that make up our feces).

Do you have to continually eat your fermented foods to maintain your bacterial population in your gut since you eat so low fiber?

What about fermented veggies? I almost always have homemade sourcraut in my fridge and it is what I usually have with my stake.It is not so sour and salty as the one in the store and could be eaten in place of a salad. My mother going even further and regularly consume fermented eggplants, tomatoes and cucumbers

Peter,Thanks for the reference to Leib's views on oxysterols. I find it convincing too, and it's interesting that he notes that glucose promotes the crystallization of cholesterol. Also interesting were his comments about oxysterols being progressively eliminated from the human diet as refrigeration technology improved. I hadn't considered the amount of oxysterols that might form in eggs, butter or yogurt at even room temperature, so with this in mind, it's easy to imagine we've been adapted to this for some time.

Also, it was really cool to hear Gary Taubes mention Hyperlipid in both parts of his new interview with Jimmy Moore. Did you have a chance to listen to it yet?

Peter: I have been reading your posts starting at the beginning and I have a question from an old post about your use of dextrose powder as a sweetener. Does the dextrose cause less of an insulin spike than say sucrose and/or fructose? Thanks for great work. Ron

My husband has a theory that prehistoric people started to eat plans because people and plants have similar enemies - parasites in human case. As a prove he claims that people in a hot climate like India and Malaysia consume o lot of spices and consider it to be healthy.His theory looks convincing. Primates like chimpanzees seek particular plants in order to get reed of internal parasites. Prehistoric people had to do the same. Why else we eat garlic, hot peppers, onion, mustard?Peter, did you ever witness such behavior in animals?

About Me

I am Petro Dobromylskyj, always known as Peter. I'm a vet, trained at the RVC, London University. I was fortunate enough to intercalate a BSc degree in physiology in to my veterinary degree. I was even more fortunate to study under Patrick Wall at UCH, who set me on course to become a veterinary anaesthetist, mostly working on acute pain control. That led to the Certificate then Diploma in Veterinary Anaesthesia and enough publications to allow me to enter the European College of Veterinary Anaesthesia and Analgesia as a de facto founding member. Anaesthesia teaches you a lot. Basic science is combined with the occasional need to act rapidly. Wrong decisions can reward you with catastrophe in seconds. Thinking is mandatory.
I stumbled on to nutrition completely by accident. Once you have been taught to think, it's hard to stop. I think about lots of things. These are some of them.

Organisation (or lack of it)!

The "labels" function on this blog has been used to function as an index and I've tended to group similar subjects together by using labels starting with identical text. If they're numbered within a similar label, start with (1). The archive is predominantly to show the posts I've put up in the last month, if people want to keep track of recent goings on. I might change it to the previous week if I ever get to time to put up enough posts in a week to justify it. That seems to be the best I can do within the limits of this blogging software!